7-151181334-G-C

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_Strong BP6_Very_Strong BS2

The NM_001142459.2(ASB10):c.709C>G(p.Arg237Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.007 in 1,613,200 control chromosomes in the GnomAD database, including 56 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0049 (5 hom., cov: 32)
  • Exomes 𝑓: 0.0072 (51 hom.)
• Consequence: ASB10 NM_001142459.2 missense
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 1.70

Genes affected

ASB10 (HGNC:17185): (ankyrin repeat and SOCS box containing 10) The protein encoded by this gene is a member of the ankyrin repeat and SOCS box-containing (ASB) family of proteins. The SOCS box serves to couple suppressor of cytokine signaling (SOCS) proteins and their binding partners with the elongin B and C complex, possibly targeting them for degradation. Multiple alternatively spliced transcript variants have been described for this gene. [provided by RefSeq, Dec 2008]

ACMG classification

Verdict is Benign. Variant got -16 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.012391508).
• BP6: Variant 7-151181334-G-C is Benign according to our data. Variant chr7-151181334-G-C is described in ClinVar as [Likely_benign]. Clinvar id is 783008.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS2: High AC in GnomAd at 748 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ASB10	NM_001142459.2	c.709C>G	p.Arg237Gly	missense_variant	3/6	ENST00000420175.3
ASB10	NM_080871.4	c.664C>G	p.Arg222Gly	missense_variant	3/6
ASB10	NM_001142460.1	c.709C>G	p.Arg237Gly	missense_variant	3/5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ASB10	ENST00000420175.3	c.709C>G	p.Arg237Gly	missense_variant	3/6	1	NM_001142459.2	P4
ASB10	ENST00000275838.5	c.709C>G	p.Arg237Gly	missense_variant	3/5	1
ASB10	ENST00000377867.7	c.664C>G	p.Arg222Gly	missense_variant	3/6	2		A1

Frequencies

GnomAD3 genomes AF: 0.00491 AC: 748 AN: 152202 Hom.: 5 Cov.: 32

Gnomad AFR AF: 0.00159

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00582

Gnomad ASJ AF: 0.000576

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.00786

Gnomad FIN AF: 0.000188

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.00784

Gnomad OTH AF: 0.00717

GnomAD3 exomes AF: 0.00465 AC: 1161 AN: 249530 Hom.: 5 AF XY: 0.00505 AC XY: 684 AN XY: 135520

Gnomad AFR exome AF: 0.000685

Gnomad AMR exome AF: 0.00284

Gnomad ASJ exome AF: 0.0000999

Gnomad EAS exome AF: 0.0000545

Gnomad SAS exome AF: 0.00846

Gnomad FIN exome AF: 0.000416

Gnomad NFE exome AF: 0.00672

Gnomad OTH exome AF: 0.00459

GnomAD4 exome AF: 0.00722 AC: 10546 AN: 1460880 Hom.: 51 Cov.: 34 AF XY: 0.00715 AC XY: 5196 AN XY: 726740

Gnomad4 AFR exome AF: 0.00125

Gnomad4 AMR exome AF: 0.00306

Gnomad4 ASJ exome AF: 0.000344

Gnomad4 EAS exome AF: 0.0000252

Gnomad4 SAS exome AF: 0.00766

Gnomad4 FIN exome AF: 0.000610

Gnomad4 NFE exome AF: 0.00833

Gnomad4 OTH exome AF: 0.00614

GnomAD4 genome AF: 0.00491 AC: 748 AN: 152320 Hom.: 5 Cov.: 32 AF XY: 0.00454 AC XY: 338 AN XY: 74494

Gnomad4 AFR AF: 0.00159

Gnomad4 AMR AF: 0.00582

Gnomad4 ASJ AF: 0.000576

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.00787

Gnomad4 FIN AF: 0.000188

Gnomad4 NFE AF: 0.00784

Gnomad4 OTH AF: 0.00710

Alfa AF: 0.00385 Hom.: 0

Bravo AF: 0.00486

TwinsUK AF: 0.00782 AC: 29

ALSPAC AF: 0.0109 AC: 42

ESP6500AA AF: 0.00113 AC: 5

ESP6500EA AF: 0.00709 AC: 61

ExAC AF: 0.00433 AC: 525

Asia WGS AF: 0.00289 AC: 10 AN: 3478

EpiCase AF: 0.00802

EpiControl AF: 0.00676

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Oct 01, 2023	ASB10: BP4, BS2 -
Benign, criteria provided, single submitter	clinical testing	Invitae	Oct 27, 2023	- -

Glaucoma 1, open angle, F Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Fulgent Genetics, Fulgent Genetics

Dec 21, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.15
BayesDel_addAF	Benign	-0.38	T
BayesDel_noAF	Benign	-0.31
Cadd	Benign	21
Dann	Uncertain	1.0
Eigen	Benign	0.13
Eigen_PC	Benign	0.18
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Uncertain	0.96	D;D;D
M_CAP	Benign	0.017	T
MetaRNN	Benign	0.012	T;T;T
MetaSVM	Benign	-0.92	T
MutationAssessor	Benign	1.0	L;.;L
MutationTaster	Benign	0.99	N;N;N;N;N
PrimateAI	Benign	0.41	T
PROVEAN	Uncertain	-2.6	D;D;D
REVEL	Benign	0.27
Sift	Benign	0.30	T;T;T
Sift4G	Benign	0.29	T;T;T
Polyphen		0.41, 0.64	.;B;P
Vest4		0.48
MVP		0.63
MPC		0.067
ClinPred		0.027	T
GERP RS		3.3
Varity_R		0.15
gMVP		0.21

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs61735708; hg19: chr7-150878421; COSMIC: COSV104997148;